CN110573532B - TGF-β 受体胞外域融合分子及其用途 - Google Patents
TGF-β 受体胞外域融合分子及其用途 Download PDFInfo
- Publication number
- CN110573532B CN110573532B CN201880025527.6A CN201880025527A CN110573532B CN 110573532 B CN110573532 B CN 110573532B CN 201880025527 A CN201880025527 A CN 201880025527A CN 110573532 B CN110573532 B CN 110573532B
- Authority
- CN
- China
- Prior art keywords
- polypeptide construct
- seq
- tgf
- fold
- nucleic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000004927 fusion Effects 0.000 title claims description 49
- 108091005735 TGF-beta receptors Proteins 0.000 title description 11
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 title description 11
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 152
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 152
- 229920001184 polypeptide Polymers 0.000 claims abstract description 151
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims abstract description 41
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims abstract description 41
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims abstract description 41
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 26
- 230000014509 gene expression Effects 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 10
- 201000011510 cancer Diseases 0.000 claims abstract description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 31
- 108020004707 nucleic acids Proteins 0.000 claims description 27
- 102000039446 nucleic acids Human genes 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 21
- 239000013598 vector Substances 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 150000001413 amino acids Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 230000009261 transgenic effect Effects 0.000 claims description 9
- 102000001708 Protein Isoforms Human genes 0.000 claims description 8
- 108010029485 Protein Isoforms Proteins 0.000 claims description 8
- 230000028327 secretion Effects 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 230000003389 potentiating effect Effects 0.000 claims description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 238000012258 culturing Methods 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 18
- 239000003446 ligand Substances 0.000 abstract description 18
- 230000003472 neutralizing effect Effects 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 12
- 230000003176 fibrotic effect Effects 0.000 abstract description 5
- 230000004913 activation Effects 0.000 abstract 1
- 206010063836 Atrioventricular septal defect Diseases 0.000 description 48
- 210000004027 cell Anatomy 0.000 description 41
- 238000001211 electron capture detection Methods 0.000 description 38
- 108090000623 proteins and genes Proteins 0.000 description 26
- 235000018102 proteins Nutrition 0.000 description 25
- 102000004169 proteins and genes Human genes 0.000 description 25
- 108020001507 fusion proteins Proteins 0.000 description 23
- 102000037865 fusion proteins Human genes 0.000 description 23
- 239000000178 monomer Substances 0.000 description 19
- 210000004899 c-terminal region Anatomy 0.000 description 18
- 238000006386 neutralization reaction Methods 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 238000000746 purification Methods 0.000 description 14
- 102000003815 Interleukin-11 Human genes 0.000 description 12
- 238000001542 size-exclusion chromatography Methods 0.000 description 12
- 239000012634 fragment Substances 0.000 description 11
- 230000000670 limiting effect Effects 0.000 description 11
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 10
- 230000004614 tumor growth Effects 0.000 description 9
- 125000003275 alpha amino acid group Chemical group 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 206010009944 Colon cancer Diseases 0.000 description 6
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 6
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 6
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 6
- 201000001441 melanoma Diseases 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000001747 exhibiting effect Effects 0.000 description 5
- 239000000710 homodimer Substances 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 description 3
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 206010031243 Osteogenesis imperfecta Diseases 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 229940049595 antibody-drug conjugate Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- SXTAYKAGBXMACB-UHFFFAOYSA-N methionine sulfoximine Chemical compound CS(=N)(=O)CCC(N)C(O)=O SXTAYKAGBXMACB-UHFFFAOYSA-N 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 101150083745 preT gene Proteins 0.000 description 2
- 239000013014 purified material Substances 0.000 description 2
- 239000010979 ruby Substances 0.000 description 2
- 229910001750 ruby Inorganic materials 0.000 description 2
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000010972 statistical evaluation Methods 0.000 description 2
- 239000011885 synergistic combination Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000007492 two-way ANOVA Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 102100026818 Inhibin beta E chain Human genes 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 206010028594 Myocardial fibrosis Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000004060 Transforming Growth Factor-beta Type II Receptor Human genes 0.000 description 1
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 101150042295 arfA gene Proteins 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012537 formulation buffer Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- -1 methionine sulfoxide imine Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 101150087557 omcB gene Proteins 0.000 description 1
- 101150115693 ompA gene Proteins 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 108700015048 receptor decoy activity proteins Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762465969P | 2017-03-02 | 2017-03-02 | |
| US62/465,969 | 2017-03-02 | ||
| US201762468586P | 2017-03-08 | 2017-03-08 | |
| US62/468,586 | 2017-03-08 | ||
| PCT/IB2018/051320 WO2018158727A1 (en) | 2017-03-02 | 2018-03-01 | Tgf-β-receptor ectodomain fusion molecules and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110573532A CN110573532A (zh) | 2019-12-13 |
| CN110573532B true CN110573532B (zh) | 2024-04-16 |
Family
ID=63370634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201880025527.6A Active CN110573532B (zh) | 2017-03-02 | 2018-03-01 | TGF-β 受体胞外域融合分子及其用途 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US11866481B2 (de) |
| EP (1) | EP3589663A4 (de) |
| JP (2) | JP7231553B2 (de) |
| KR (2) | KR20240027854A (de) |
| CN (1) | CN110573532B (de) |
| AU (1) | AU2018228435A1 (de) |
| CA (1) | CA3055156A1 (de) |
| IL (2) | IL305536A (de) |
| MX (1) | MX2019010392A (de) |
| WO (1) | WO2018158727A1 (de) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015027082A1 (en) | 2013-08-22 | 2015-02-26 | Acceleron Pharma, Inc. | Tgf-beta receptor type ii variants and uses thereof |
| CA2994413A1 (en) | 2015-08-04 | 2017-02-09 | Acceleron Pharma, Inc. | Methods for treating myeloproliferative disorders |
| KR20240027854A (ko) | 2017-03-02 | 2024-03-04 | 내셔날 리서치 카운실 오브 캐나다 | Tgf-β-수용체 엑토도메인 융합 분자 및 그의 용도 |
| HRP20230706T1 (hr) | 2017-05-04 | 2023-10-13 | Acceleron Pharma Inc. | Fuzijski proteini tgf-beta receptora tipa ii i njihove upotrebe |
| MX2021009175A (es) | 2019-01-30 | 2021-09-14 | Scholar Rock Inc | Inhibidores especificos del complejo de ltbp de tgf? y usos de los mismos. |
| WO2020210596A1 (en) * | 2019-04-10 | 2020-10-15 | University Of Kentucky Research Foundation | Modified prostate apoptosis response-4 (par-4) polypeptide, and methods of production and use |
| CA3167427A1 (en) | 2020-01-11 | 2021-07-15 | Scholar Rock, Inc. | Tgfb inhibitors and use thereof |
| CA3166328A1 (en) | 2020-01-11 | 2021-07-15 | Scholar Rock, Inc. | Tgf-beta inhibitors and use thereof |
| KR20220143063A (ko) | 2020-02-19 | 2022-10-24 | 남미 테라퓨틱스, 인크. | 암의 치료에 유용한 TGFβ 길항제 전구약물을 함유하는 제제화된 및/또는 공동-제제화된 리포솜 조성물 및 그의 방법 |
| CN115956085A (zh) * | 2020-06-12 | 2023-04-11 | 百时美施贵宝公司转化生长因子β有限公司 | 转化生长因子β(TGFβ)结合剂及其用途 |
| WO2022204581A2 (en) | 2021-03-26 | 2022-09-29 | Scholar Rock, Inc. | Tgf-beta inhibitors and use thereof |
| WO2022256723A2 (en) | 2021-06-03 | 2022-12-08 | Scholar Rock, Inc. | Tgf-beta inhibitors and therapeutic use thereof |
| KR20240025533A (ko) * | 2021-06-24 | 2024-02-27 | 브리스톨-마이어스 스큅 컴퍼니 | 질병 치료를 위한 형질전환 성장 인자-베타 리간드 트랩 |
| US11945856B2 (en) | 2022-01-28 | 2024-04-02 | 35Pharma Inc. | Activin receptor type IIB variants and uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1257545A (zh) * | 1997-04-18 | 2000-06-21 | 拜奥根有限公司 | Ⅱ型TGF－β受体/免疫球蛋白恒定区融合蛋白 |
| WO2012142515A2 (en) * | 2011-04-13 | 2012-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
| CN105658672A (zh) * | 2013-08-22 | 2016-06-08 | 阿塞勒隆制药公司 | TGF-β受体II型变体及其用途 |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69332026T2 (de) | 1992-10-29 | 2002-10-31 | Celtrix Pharma | Typ ii tgf-beta-bindendes rezeptorfragment als therapeutisches mittel |
| DE69434520T3 (de) | 1993-07-30 | 2009-10-15 | Affymax, Inc., Palo Alto | Biotinylierung von proteinen |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| CA2330939A1 (en) * | 1998-06-16 | 1999-12-23 | Biogen, Inc. | Variant type ii tgf-beta receptor fusion proteins and methods |
| CA2407956A1 (en) | 2000-05-03 | 2001-11-08 | Amgen Inc. | Modified peptides as therapeutic agents |
| EP1452601A1 (de) | 2003-02-28 | 2004-09-01 | Roche Diagnostics GmbH | Verstärkte Expression von Fusionspolypeptiden durch einen biotinylierten Marker |
| WO2005028517A2 (en) | 2003-05-09 | 2005-03-31 | The General Hospital Corporation | SOLUBLE TGF-β TYPE III RECEPTOR FUSION PROTEINS |
| AU2005235635B2 (en) | 2004-04-21 | 2010-11-18 | Alexion Pharmaceuticals, Inc. | Bone delivery conjugates and method of using same to target proteins to bone |
| US7795389B2 (en) | 2004-09-28 | 2010-09-14 | The Board Of Regents Of The University Of Texas System | Antagonizing TGF-beta activity with various ectodomains TGF-beta receptors used in combination or as fusion proteins |
| CA2597925A1 (en) | 2005-02-16 | 2006-08-24 | The General Hospital Corporation | Use of a human hemojuvelin product to regulate hepcidin-mediated iron metabolism |
| EP2046374A4 (de) | 2006-07-10 | 2010-05-05 | Biogen Idec Inc | Zusammensetzungen und verfahren zur wachstumshemmung von smad4-defizienten tumoren |
| US8318135B2 (en) | 2007-03-19 | 2012-11-27 | National Research Council Of Canada | Antagonist of ligands and uses thereof |
| JP2010529859A (ja) * | 2007-06-15 | 2010-09-02 | ジェンザイム、コーポレーション | ＴＧＦ−βＩＩ型受容体の２つのＴＧＦ−β結合ドメインを含有する融合タンパク質 |
| WO2010031168A1 (en) | 2008-09-17 | 2010-03-25 | National Research Council Of Canada | HETERO-MULTIVALENT BINDING AGENTS FOR MEMBERS OF THE TGFβ SUPERFAMILY |
| WO2010003118A1 (en) | 2008-07-02 | 2010-01-07 | Trubion Pharmaceuticals, Inc. | Tgf-b antagonist multi-target binding proteins |
| KR101558642B1 (ko) | 2009-02-24 | 2015-10-12 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | Ｔｇｆ-베타 슈퍼패밀리의 설계자 리간드 |
| JP5918129B2 (ja) | 2009-06-22 | 2016-05-18 | メディミューン，エルエルシー | 部位特異的共役のための操作されたＦｃ領域 |
| RU2413769C1 (ru) | 2009-12-24 | 2011-03-10 | Учреждение Российской академии наук Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН | РЕКОМБИНАНТНАЯ ПЛАЗМИДНАЯ ДНК pET-32a, КОДИРУЮЩАЯ ГЕН ЛИГАНД-СВЯЗЫВАЮЩЕГО ДОМЕНА РЕЦЕПТОРА II ТИПА ТРАНСФОРМИРУЮЩЕГО ФАКТОРА РОСТА-β ЧЕЛОВЕКА (TβRII), ШТАММ БАКТЕРИЙ Escherichia coli - ПРОДУЦЕНТ СЛИТНОГО БЕЛКА ТИОРЕДОКСИН/TβRII И СПОСОБ РЕНАТУРАЦИИ И ОЧИСТКИ ЦЕЛЕВОГО БЕЛКА TβRII |
| EP2542590B2 (de) | 2010-03-05 | 2020-04-01 | The Johns Hopkins University | Zusammensetzungen und verfahren für gezielte immunmodulatorische antikörper und fusionsproteine |
| CA2819187A1 (en) | 2010-11-29 | 2012-06-07 | National Research Council Of Canada | Covalently dimerized bivalent binding agents |
| CN102850458B (zh) | 2011-06-28 | 2014-10-01 | 华博生物医药技术（上海）有限公司 | 新型重组双功能融合蛋白及其制法和用途 |
| US9782452B2 (en) | 2011-11-22 | 2017-10-10 | Cornell University | Methods for stimulating hematopoietic recovery by inhibiting TGFβ signaling |
| CN104334573A (zh) | 2012-04-30 | 2015-02-04 | 比奥孔有限公司 | 靶向/免疫调节性融合蛋白及其制造方法 |
| NZ711445A (en) | 2013-03-12 | 2018-06-29 | Biocon Ltd | Fusion immunomodulatory proteins and methods for making same |
| CA2931309C (en) * | 2013-11-21 | 2022-06-21 | The Brigham And Women's Hospital, Inc. | Compositions and methods for treating pulmonary hypertension |
| JP6731346B2 (ja) | 2014-02-10 | 2020-07-29 | メルク パテント ゲーエムベーハー | 標的ＴＧＦβ阻害 |
| CN106794233B (zh) | 2014-08-01 | 2021-11-12 | 布里格姆及妇女医院股份有限公司 | 与肺动脉高压的治疗有关的组合物和方法 |
| JP6631865B2 (ja) * | 2014-08-11 | 2020-01-15 | 日本化薬株式会社 | ＴＧＦβ阻害機能を持つキメラタンパク質 |
| EP3344660A4 (de) | 2015-08-31 | 2019-07-03 | National Research Council of Canada | Tgf-beta-rezeptor-ektodomänenfusionsmoleküle und verwendungen davon |
| KR20240027854A (ko) | 2017-03-02 | 2024-03-04 | 내셔날 리서치 카운실 오브 캐나다 | Tgf-β-수용체 엑토도메인 융합 분자 및 그의 용도 |
| HRP20230706T1 (hr) | 2017-05-04 | 2023-10-13 | Acceleron Pharma Inc. | Fuzijski proteini tgf-beta receptora tipa ii i njihove upotrebe |
| TW202003011A (zh) | 2018-03-26 | 2020-01-16 | 美商艾爾特生物科技責任有限公司 | 抗ＰＤＬ１、ＩＬ－１５及ＴＧＦ－β受體組合分子 |
| BR112020022145A2 (pt) | 2018-05-04 | 2021-01-26 | Merck Patent Gmbh | inibição combinada de pd-1/pd-l1, tgfbeta e dna-pk para o tratamento de câncer |
| CN113301961A (zh) | 2018-11-01 | 2021-08-24 | 默克专利有限公司 | 给予抗tim-3抗体的方法 |
| WO2020146345A1 (en) | 2019-01-07 | 2020-07-16 | Children's Medical Center Corporation | Methods of treating cancer using lsd1 inhibitors and/or tgf-beta inhibitors in combination with immunotherapy |
| US20230056470A1 (en) | 2019-12-20 | 2023-02-23 | Novartis Ag | Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
| CN115956085A (zh) | 2020-06-12 | 2023-04-11 | 百时美施贵宝公司转化生长因子β有限公司 | 转化生长因子β(TGFβ)结合剂及其用途 |
| KR20240025533A (ko) | 2021-06-24 | 2024-02-27 | 브리스톨-마이어스 스큅 컴퍼니 | 질병 치료를 위한 형질전환 성장 인자-베타 리간드 트랩 |
-
2018
- 2018-03-01 KR KR1020247005491A patent/KR20240027854A/ko active Application Filing
- 2018-03-01 KR KR1020197028434A patent/KR20190129896A/ko not_active IP Right Cessation
- 2018-03-01 EP EP18760608.2A patent/EP3589663A4/de active Pending
- 2018-03-01 MX MX2019010392A patent/MX2019010392A/es unknown
- 2018-03-01 US US16/490,335 patent/US11866481B2/en active Active
- 2018-03-01 JP JP2019547490A patent/JP7231553B2/ja active Active
- 2018-03-01 IL IL305536A patent/IL305536A/en unknown
- 2018-03-01 AU AU2018228435A patent/AU2018228435A1/en active Pending
- 2018-03-01 CN CN201880025527.6A patent/CN110573532B/zh active Active
- 2018-03-01 WO PCT/IB2018/051320 patent/WO2018158727A1/en unknown
- 2018-03-01 IL IL268995A patent/IL268995B2/en unknown
- 2018-03-01 CA CA3055156A patent/CA3055156A1/en active Pending
-
2023
- 2023-02-15 JP JP2023021751A patent/JP2023056001A/ja active Pending
- 2023-08-29 US US18/457,588 patent/US20240101641A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1257545A (zh) * | 1997-04-18 | 2000-06-21 | 拜奥根有限公司 | Ⅱ型TGF－β受体/免疫球蛋白恒定区融合蛋白 |
| WO2012142515A2 (en) * | 2011-04-13 | 2012-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
| CN105658672A (zh) * | 2013-08-22 | 2016-06-08 | 阿塞勒隆制药公司 | TGF-β受体II型变体及其用途 |
Non-Patent Citations (1)
| Title |
|---|
| Engineering and Therapeutic Application of Single-Chain Bivalent TGF-b Family Traps;John C. Zwaagstra et al;《Molecular Cancer Therapeutics》;20120731;第11卷(第7期);第1477-1487页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3055156A1 (en) | 2018-09-07 |
| IL268995B1 (en) | 2023-10-01 |
| IL268995B2 (en) | 2024-02-01 |
| US20220204587A1 (en) | 2022-06-30 |
| CN110573532A (zh) | 2019-12-13 |
| EP3589663A4 (de) | 2020-10-21 |
| IL268995A (en) | 2019-10-31 |
| MX2019010392A (es) | 2019-12-02 |
| US11866481B2 (en) | 2024-01-09 |
| WO2018158727A1 (en) | 2018-09-07 |
| AU2018228435A1 (en) | 2019-10-03 |
| JP7231553B2 (ja) | 2023-03-01 |
| RU2019129636A (ru) | 2021-04-02 |
| RU2019129636A3 (de) | 2021-07-05 |
| KR20190129896A (ko) | 2019-11-20 |
| US20240101641A1 (en) | 2024-03-28 |
| JP2020510434A (ja) | 2020-04-09 |
| KR20240027854A (ko) | 2024-03-04 |
| IL305536A (en) | 2023-10-01 |
| JP2023056001A (ja) | 2023-04-18 |
| EP3589663A1 (de) | 2020-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110573532B (zh) | TGF-β 受体胞外域融合分子及其用途 | |
| US11919931B2 (en) | Anti-cancer fusion polypeptide capable of binding both CD137 and glypican-3 (GPC3) | |
| CN110461871B (zh) | 白蛋白结合结构域融合蛋白 | |
| US11827697B2 (en) | Anti-PD-1/anti-VEGF natural antibody structure like heterodimeric form bispecific antibody and preparation thereof | |
| CN107709355B (zh) | 单链cd40受体激动剂蛋白 | |
| CN108430492B (zh) | 单链cd27受体激动剂蛋白 | |
| US20180280474A1 (en) | Treatment of bile acid disorders | |
| CA3002741A1 (en) | Single-chain gitr-receptor agonist proteins | |
| WO2023222035A1 (zh) | 抗tigit抗体与il2的融合蛋白或其变体及其应用 | |
| KR20160113268A (ko) | 이기능 융합단백질,이의 제조방법 및 용도 | |
| AU2021324738B2 (en) | Fusion protein comprising IL-12 and anti-fap antibody, and use thereof | |
| CN101914161B (zh) | 抑制肿瘤生长的融合蛋白HGFα-Fc及其用途 | |
| RU2797464C2 (ru) | Слитые молекулы эктодомена рецептора tgf-бета и их применения | |
| WO2021031736A1 (zh) | 多功能抗体、其制备及其用途 | |
| KR20220062084A (ko) | 면역 복합체 매개된 콩팥 장애의 치료를 위한 재조합 IgG Fc 다량체 | |
| CN114615989A (zh) | 用于治疗癌症的靶向整联蛋白的打结素-fc融合体与抗cd47抗体的组合 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |